Interplay between Dose and Frequency of GnRH Administration in Determining Pituitary Gonadotropin ResponsivenessHughes V.A. · Boepple P.A. · Crowley, Jr. W.F. · Seminara S.B.
Harvard Reproductive Endocrine Sciences Center and Reproductive Endocrine Unit, Department of Medicine and Department of Pediatrics, Massachusetts General Hospital, Boston, Mass., USA
Background/Aims: The dose, frequency and contour of GnRH stimulation of the pituitary gonadotrope have been shown to be independent variables influencing pituitary LH secretion. The dynamic interaction between these variables during physiological and pathophysiological states has yet to be examined. Methods: Twelve men with GnRH deficiency and idiopathic hypogonadotropic hypogonadism undergoing GnRH therapy participated in a series of studies in which 2 log orders of GnRH doses (2.5–250 ng/kg) were administered at frequencies varying from 0.5 to 8 hourly. Pituitary responses were characterized by pulse amplitudes and nadirs. The relative sensitivity of the gonadotrope to GnRH was defined as that dose of GnRH capable of eliciting an LH pulse amplitude equal to the mean LH amplitude in normal men. Results: As GnRH stimulation of the gonadotrope slowed from 0.5 to 8 hourly, pulse amplitudes of LH increased whereas mean nadirs decreased (p < 0.05). Unique, curvilinear dose-response curves were found for each frequency that demonstrated an increasing slope (p < 0.03) as the frequency of GnRH stimulation slowed. Thus, the relative sensitivity of the gonadotrope increased as the frequency of GnRH stimulation decreased over the range of physiological frequencies tested. Conclusions: We conclude that a delicate interplay exists between the dose and frequency of GnRH stimulation of the gonadotrope that determines pituitary LH gonadotropin responsiveness in the human. Slower frequencies favor increased LH release largely due to decreasing LH nadirs and improved sensitivity of the gonadotropes to GnRH stimulation.
© 2007 S. Karger AG, Basel
Supported by NICHD R01-15788-22 and NIH RR1066.
Received: August 30, 2007
Accepted after revision: October 26, 2007
Number of Print Pages : 9
Number of Figures : 4, Number of Tables : 3, Number of References : 22
Neuroendocrinology (International Journal for Basic and Clinical Studies on Neuroendocrine Relationships)
Vol. 87, No. 3, Year 2008 (Cover Date: April 2008)
Journal Editor: Millar R.P. (Edinburgh)
ISSN: 0028–3835 (Print), eISSN: 1423–0194 (Online)
For additional information: http://www.karger.com/NEN